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First published online October 27, 2004

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Acetylcholine signals change of direction

A variety of stimuli cause cells to move (chemokinesis); some also tell them where to go (chemotaxis). The signalling mechanisms that drive these two types of migration – random and directed – are usually similar. Sergei Grando and co-workers show that in the case of acetylcholine, however, they differ significantly (see p. 5665). Acetylcholine regulates migration of keratinocytes in the skin by binding to nicotinic receptors (nAChRs). Grando and co-workers have used a combination of receptor antagonists, antisense oligonucleotides directed against different nAChRs and cells from nAChR-knockout mice to examine the underlying mechanisms. They demonstrate that the 3 nAChR subtype controls chemokinesis whereas the 7 subtype controls chemotaxis. Moreover, they find that 3-nAChR-induced chemokinetic signalling leads to activation of protein kinase C (PKC), the GTPase RhoA and its effector ROCK. By contrast, 7-nAChR-induced chemotactic signalling involves conventional PKC isoforms, Ca²⁺, PI 3-kinase and the GTPases Rac and Cdc42. Since keratinocyte migration is central to wound healing and implicated in metastasis, these findings not only shed light on migration mechanisms but also have potential clinical implications.

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Related articles in JCS:

Differential regulation of keratinocyte chemokinesis and chemotaxis through distinct nicotinic receptor subtypes

Alex I. Chernyavsky, Juan Arredondo, Lisa M. Marubio, and Sergei A. Grando
JCS 2004 117: 5665-5679. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?